Pulse generator for cranial nerve stimulation

ABSTRACT

A system for trigeminal nerve stimulation includes a pulse generator, which includes a user control configured to receive a user adjustment and a microcontroller configured to receive electric stimulation parameters and operate the pulse generator to produce electrical pulses according to the electric stimulation parameters during a treatment session. A method for nerve stimulation includes receiving, by a pulse generator, electric stimulation parameters, and producing, by the pulse generator, electrical pulses according to electric stimulation parameters during a treatment session. The electric stimulation parameters include at least one user-set parameter, which includes a current amplitude that is responsive to the user adjustment of the user control, and at least one physician-set parameter, which includes an upper bound and a lower bound for the current amplitude.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.13/990,348, now issued as U.S. Pat. No. 9,364,674, which was theNational Stage of International Application No. PCT/US2011/062714, filedNov. 30, 2011, which claims the benefit of U.S. Provisional ApplicationNo. 61/418,382, filed Nov. 30, 2010, all of which are incorporatedherein by reference in their entirety.

TECHNICAL FIELD

The present disclosure generally relates to external neurostimulatordevices and methods of using the same and more particularly relates toexternal neurostimulator devices configured to stimulate the superficial(cutaneous) sensory branches of cranial nerves.

BACKGROUND

Currently available surgical treatment methods for certain medicaldisorders, such as epilepsy or other seizure related disorders, mayinclude stimulation of the nervous system by vagus nerve stimulation(VNS), which has been approved by the U.S. Food and Drug Administration(FDA). In this method, stimulating electrodes are surgically implantedin contact with the vagus nerve as it passes through the neck. Inaddition to complications related to anesthesia, potential forinfection, cost, and other adverse events with VNS, many of the subjectswho undergo VNS treatments do not achieve relief, and there is noreliable predictor of good outcomes from the implanted VNS device.

Other approaches to neuromodulation are the focus of on-going research.For example, implantable approaches are also being studied, includingdeep brain stimulation (DBS) of specific brain regions, and intracranialstimulation of the same via a device which monitors brain activity anddelivers stimuli as needed. However, the risks of DBS include infection,hemorrhage, and injury to deep brain structures.

In some clinical situations, electroconvulsive therapy (ECT) andrepetitive transcranial magnetic stimulation (rTMS) have been used forneurological and psychiatric conditions. Traditionally, brainstimulation has been a primary treatment alternative to medications andpsychotherapy, and ECT has been the dominant brain stimulation approachsince the first part of the 20th century. However, ECT carries risks ofmemory and other cognitive side effects, considerable cost, and risks ofanesthesia.

Many of the above-described methods are invasive and may haveconsiderable costs and side effects. Further, a substantial percentageof patients do not recover from or get adequate lasting relief for thecondition or disorder despite multiple trials of pharmaceutical orsurgical treatment.

The information included in this Background section of thespecification, including any references cited herein and any descriptionor discussion thereof, is included for technical reference purposes onlyand is not to be regarded as subject matter by which the scope of theinvention is to be bound.

SUMMARY

One aspect of the subject matter of the present disclosure addresses theaforementioned needs by providing a system and device configured tostimulate the trigeminal nerve that is minimally invasive and hasreduced side effects in comparison with other neuromodulationapproaches.

Disclosed herein is a system for trigeminal nerve stimulation. In oneembodiment, the system includes a storage medium, a pulse generatorcommunicatively coupled to the storage medium, a power source coupled tothe pulse generator, and at least one electrode communicatively coupledto the pulse generator. The pulse generator includes a microcontrollerwhich executes instructions from the storage medium and themicrocontroller is configured to perform at least one of the followingoperations: produce electrical pulses having defined characteristics,record a log of use and anomalous events, restrict use to a specifiedindividual, interface with electrodes, provide a signal to the specifiedindividual indicating operational conditions and trouble conditions, andprovide a signal to the specified individual indicating an end of atreatment period. In some embodiments, the system may further include apower supply or charging station. The power source may be a battery,such as a rechargeable battery.

Disclosed herein is a pulse generator for trigeminal nerve stimulation.In one embodiment, the generator includes a body having a front and backportion and includes at least one electrode channel. The pulse generatoralso includes a power source. The pulse generator also includes at leastone microcontroller executing instructions from a storage medium and themicrocontroller is configured to perform at least one of the followingoperations: produce electrical pulses having defined characteristics,record a log of use and anomalous events, restrict use to a specifiedindividual, interface with electrodes, provide a signal to the specifiedindividual indicating operational conditions and trouble conditions, andprovide a signal to the specified individual indicating an end of atreatment period. The pulse generator further includes a displayconfigured to provide a graphical user interface and at least one usercontrol feature configured to allow a user to control at least oneoperation of the pulse generator. The pulse generator may furtherinclude a power inlet port defined in the body. In one embodiment, thebody has dimensions of approximately 115 mm (4.5 in) H×69 mm (2.7 in)W×27 mm (1.1 in) D and a weight of 145 g (5.1 oz) without a battery. Insome embodiments, the power source may be a battery and the body mayinclude at least one battery cavity defined in the back portion of thebody that is configured to accept a battery. In one embodiment, the bodyis plastic, metal alloy or composite material. In one aspect, themicrocontroller limits output current and the current is limited toapproximately less than 35 mA. In various embodiments, the currentoutput has an upper limit of approximately 10 mA, 7 mA or 5 mA. In someembodiments, the current output has a lower limit of approximately 2.5mA. In some embodiments, the current output is fixed at approximately 5mA. In one embodiment, the microcontroller is configured to deliver (ordelivers) a true square-wave charge-balanced output signal or anon-rectangular output signal. In one aspect, the microcontrollerproduces electrical pulses having the following characteristics:frequency 1-300 Hz, pulse duration 50-500 μsec, duty cycle 1-100%. Inone aspect, the electrode channel comprises at least one grooveconfigured to accept at least one projection located at an end of a leadwire of the electrode assembly to form a lock and key configuration. Inone aspect, the electrode channel is keyed for a specific electrodeassembly.

Disclosed herein is a method for operating a pulse generator having aprocessing device for stimulating at least one cutaneous trigeminalnerve branch using the pulse generator. In one embodiment, the methodincludes receiving instructions from a storage medium and performing atleast one of the following operations: producing electrical pulseshaving defined characteristics, recording a log of use and anomalousevents, restricting use to a specified individual, interfacing withspecialized electrodes, providing a signal to the specified individualindicating operational conditions and trouble conditions, and providinga signal to the specified individual indicating an end of a treatmentperiod. In one aspect, the operation of restricting use to a specifiedindividual comprises requiring a patient user to provide a personalidentification number (PIN) or a biometric ID to operate the pulsegenerator. In one aspect, the PIN is a five digit number and thebiometric ID is a fingerprint. In one aspect, the operation of producingelectrical pulses having defined characteristics is performed by amicrocontroller and the characteristics are frequency 1-300 Hz, pulseduration 50-500 μsec, duty cycle 1-100%. In one aspect, the operation ofinterfacing with electrodes is performed by at least one electrodechannel defined in the pulse generator that is keyed to the electrode.

Disclosed herein is a computer-readable medium havingcomputer-executable instructions for performing a process forstimulating a branch of a trigeminal nerve. In one embodiment, theinstructions include causing a processor device to produce electricalpulses having defined characteristics, record a log of use and anomalousevents, restrict use to a specified individual, interface with specifiedelectrodes, provide a signal to the specified individual indicatingoperational conditions and trouble conditions, and provide a signal tothe specified individual indicating an end of a treatment period.

This Summary is provided to introduce a selection of concepts in asimplified form that are further described below in the DetailedDescription. This Summary is not intended to identify key features oressential features of the claimed subject matter, nor is it intended tobe used to limit the scope of the claimed subject matter. A moreextensive presentation of features, details, utilities, and advantagesof the present invention is provided in the following writtendescription of various embodiments of the invention, illustrated in theaccompanying drawings, and defined in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure, both as to its organization and manner ofoperation, may be understood by reference to the following description,taken in connection with the accompanying drawings, in which:

FIGS. 1A and 1B illustrate the location of several branches (nerves) ofthe trigeminal nerve and the location of the major foramina for thesuperficial branches of the trigeminal nerve;

FIG. 2A depicts an example of a subject wearing one embodiment of anelectrode assembly and pulse generator according to aspects of thepresent disclosure;

FIG. 2B depicts an example of a subject wearing another embodiment of anelectrode assembly and pulse generator according to aspects of thepresent disclosure;

FIG. 3A is a front perspective view of another embodiment of a pulsegenerator according to aspects of the present disclosure;

FIG. 3B is a front plan view of the pulse generator of FIG. 3A;

FIG. 3C is a left side view of the pulse generator of FIG. 3A;

FIG. 3D is a right side view of the pulse generator of FIG. 3A;

FIG. 3E-1 is a top perspective view of the pulse generator of FIG. 3A;

FIG. 3E-2 is a top plan view of the pulse generator of FIG. 3A;

FIG. 3F-1 and FIG. 3F-2 depict top plan views of the inside front andback portions of the housing of the pulse generator of FIG. 3A;

FIG. 3G is a top plan view of the inside back portion of the housingpulse generator of FIG. 3A, wherein some electrical components and adisplay are shown;

FIG. 3H is the pulse generator of FIG. 3G wherein the electricalcomponents beneath the display are shown;

FIGS. 3I-3J depict an expanded view of the electrical components shownin FIG. 3H;

FIG. 3K is a back plan view of the electrical components shown in FIGS.3I-3J;

FIG. 3L is a back plan view of the display and associated electricalcomponents of FIG. 3H;

FIG. 4 is a block diagram of the system of FIG. 3;

FIG. 5 is a flow chart illustrating one embodiment of a method foroperation of a pulse generator.

DETAILED DESCRIPTION

The present disclosure relates to a device configured for stimulation ofthe sensory branches of the trigeminal nerve in the face and forehead(trigeminal nerve stimulation or TNS). More specifically, an externalpulse generator or neurostimulator configured for stimulation of thesensory components of the ophthalmic nerve and its branches, theinfraorbital nerve and its branches, and the mentalis nerves or itsbranches, and including the supraorbital, supratrochlear, infraorbital,auriculotemporal, zygomaticotemporal, zygomaticoorbital,zygomaticofacial, nasal and infratrochlear nerves is disclosed herein.The pulse generator may be used to treat various disorders, such asneurological disorders as disclosed in, for example, U.S. applicationSer. No. 12/898,675, entitled “Systems, Devices and Methods for theTreatment of Neurological Disorders and Conditions,” filed Oct. 5, 2010,now U.S. Pat. No. 8,688,220, issued Apr. 1, 2014, and psychiatricdisorders as disclosed in, for example, U.S. application Ser. No.12/898,686 entitled “Devices, Systems and Methods for Treatment ofNeuropsychiatric Disorders,” filed Oct. 5, 2010, now U.S. Pat. No.8,380,315, issued Feb. 19, 2013, both of which are incorporated hereinby reference in their entirety.

In previous studies, a commercially available TENS unit, the EMS 7500,has been used. The TENS unit is designed to deliver currents up to 100mA, well above the levels needed for external TNS. In clinical use forTNS for epilepsy, for example, the high currents would present apotential safety hazard to patients, both for dermal injury and thepassage of current through the skull and injuring the brain parenchyma.The pulse generator or neurostimulator as disclosed herein is configuredto limit the current delivered and includes a programmablemicrocontroller to implement the features disclosed herein, therebyreducing the potential for patient injury and optimizing ease of use(user friendliness).

The pulse generator as disclosed herein includes a programmablemicrocontroller which, in various embodiments, may implement some or allof the following features: produces electrical pulses of specific,programmable characteristics; records a log of use and anomalous events;restricts use to a specified individual; interfaces with variouselectrode designs, including both subcutaneous implantable electrodedesigns, such as those described in U.S. application Ser. No.12/898,685, entitled “Extracranial Implantable Devices, Systems andMethods for the Treatment of Neuropsychiatric Disorders,” filed Oct. 5,2010, now U.S. Pat. No. 8,958,880, issued Feb. 17, 2015, and U.S.application Ser. No. 12/898,696, entitled “Extracranial ImplantableDevices, Systems and Methods for the Treatment of NeurologicalDisorders,” filed Oct. 5, 2010 and published as U.S. Patent ApplicationPublication No. 2011-0106220, both of which are incorporated herein byreference in their entirety, and cutaneous electrode designs, such asthose described in U.S. application Ser. No. 12/898,675, now issued asU.S. Pat. No. 8,688,220 and U.S. application Ser. No. 12/898,686, nowissued as U.S. Pat. No. 8,380,315, referenced herein above; signals thepatient-user (or a physician or other care provider) about operationalconditions and trouble conditions; signals the need for a physicianreprogramming visit with weekly warning signals and suspendingoperations until reprogrammed at the specified date; and is rechargeableand is sealed to protect against, for example, liquid penetration intothe internal structure of the pulse generator. In some embodiments, thepulse generator may signal a physician or other care provider over theinternet or cell phone and the communication may be in real time. Insome embodiments, the pulse generator can inform a physician or othercare provider that the patient may be having a seizure (based onprocessing implanted or external EEG data, or other physiologic datasuch as autonomic nervous system indices (e.g. heart rate variability))or that the patient has fallen (based on processing data from anaccelerometer built into the pulse generator or implanted in thepatient).

The unique anatomy of the trigeminal nerve, and its direct and indirectprojections to key areas of the brainstem, thalamus and cortex involvedwith sensory processing, attention, and autonomic function, may allowthe use of stimulation by a pulse generator as disclosed herein for avariety of neurological, psychiatric and other conditions in whichstimulation may be desirable.

For a discussion related to the trigeminal nerve, reference is now madeto FIGS. 1A-1B, which illustrate the location of several branches of thetrigeminal nerve and the location of the major foramina for thesuperficial branches of the trigeminal nerve. The trigeminal nerve isthe largest cranial nerve and has extensive connections with thebrainstem and other brain structures. As it is the fifth of the twelvecranial nerves, it is also known interchangeably as CN V. The trigeminalnerve has three major sensory branches over the face, all of which arebilateral, and highly accessible. The supraorbital nerve, or ophthalmicnerve, is frequently referred to as the V₁ division. The infraorbitalbranch, or the maxillary nerve, is commonly referred to as the V₂division. The superficial branch, or the mandibular nerve (also known asthe mentalis branch), is referred to as the V₃ division. Thesupraorbital nerve supplies sensory information about pain, temperature,and light touch to the skin of the forehead, the upper eyelid, theanterior part of the nose, and the eye. The infraorbital branch suppliessensory information about pain, temperature, and light touch sensationto the lower eyelid, cheek, and upper lip. The mentalis branch suppliessimilar sensory modalities to the jaw, tongue, and lower lip.

As can be understood from FIGS. 1A and 1B, these branches exit the skullthrough three foramina. The supraorbital nerve or ophthalmic nerve exitsat foramen 1 (the supraorbital foramen or notch), approximately 2.1-2.6cm from the nasal midline (in adults), and is located immediately abovethe orbital ridge that is near the eyebrow. The nasal nerve is adivision of the ophthalmic nerve. The infraorbital branch or maxillarynerve exits at foramen 2 (the infraorbital foramen), approximately2.4-3.0 cm from the nasal midline (in adults) and the mentalis nerveexits at foramen 3 (the mentalis foramen) approximately 2.0-2.3 cm fromthe nasal midline (in adults). Other sensory branches, including thezygomaticofacial, zygomaticoorbital, zygomaticotemporal, andauriculotemporal, arise from other foramina.

Fibers from the three major branches join together to form thetrigeminal ganglion. From there, fibers ascend into the brainstem at thelevel of the pons to synapse with the main sensory nucleus of the pons,the mesencephalic nucleus of Cranial Nerve V, and the spinal nucleus andtract of V. Pain fibers descend in the spinal nucleus and tract of V,and then ascend to the ventral posterior medial nucleus (VPM) of thethalamus and then project to the cerebral cortex. Light touch sensoryfibers are large myelinated fibers, which ascend to the ventralposterior lateral (VPL) nucleus of the thalamus. Afferent sensory fibersproject from the trigeminal nuclei to the thalamus and the cerebralcortex.

The trigeminal nucleus has projections to the nucleus tractus solitarius(NTS), the locus ceruleus, the cerebral cortex, and the vagus nerve. TheNTS receives afferents from the vagus nerve and trigeminal nerve. NTSintegrates input from multiple sources, and projects to structures inthe brainstem and forebrain, including the locus ceruleus.

The locus ceruleus is a paired nuclear structure in the dorsal pons, andis located just beneath the floor of the fourth ventricle. The locuscoeruleus has extensive axonal projections to a broad number ofbrainstem, sub-cortical and cortical structures, and is an importantpart of the reticular activating system. The locus ceruleus is a corepart of the brainstem noradrenergic pathway, and produces theneurotransmitter norepinephrine. Norepinephrine plays a key role inattention, alertness, blood pressure and heart rate regulation, anxietyand mood.

While not wishing to be bound by any particular theory, in certainembodiments, the connections between the trigeminal nerve, locuscoeruleus, nucleus and tractus solitarius, thalamus, and cerebralcortex, may be relevant to a potential role of the trigeminal nerve innumerous disorders and conditions. Thus, cutaneous stimulation of thetrigeminal nerve via a pulse generator as disclosed herein or a systemthat includes the pulse generator may be effective in the treatment ofmultiple disorders and conditions where treatment via trigeminal nervestimulation is indicated.

Accordingly, stimulation of the superficial or cutaneous branches of thetrigeminal nerve provides an avenue for non-invasive neuromodulation.Further, stimulation parameters can be tailored for the individualcondition, such that the brainstem, thalamic, or cortical structuresinvolved in the individual condition can be activated or inhibiteddepending on the pathophysiology of the condition being treated.

In one embodiment, as can be understood from FIGS. 2A-2B, a system 100for stimulation of the trigeminal nerve or a branch thereof includes anelectrode assembly 10, a neurostimulator or pulse generator 15 andelectrical cable or wire 20. The electrode assembly 10 may be configuredfor the bilateral simultaneous and asynchronous stimulation of theophthalmic nerves. In other embodiments, the electrode assembly may beconfigured for unilateral or bilateral stimulation of one or morebranches of the trigeminal nerve as disclosed elsewhere herein. Theelectrode assembly 10 may include a pair of electrodes for placement ona region of the patient's face. It can be appreciated that a singleelectrode or multiple electrodes may be used. An electrode assembly thatmay be used with the present disclosure is also described in U.S.application Ser. No. 12/898,675, now issued as U.S. Pat. No. 8,688,220and U.S. application Ser. No. 12/898,686, now issued as U.S. Pat. No.8,380,315, referenced herein above. In one embodiment, the electricalcable or wire 20 is configured to provide a physical and electrical linkbetween the generator 15 and the electrode assembly 10 via lead wires.In other embodiments, the generator 15 and the electrode assembly 10communicate wirelessly (i.e. the wire 20 and lead wires are not used).In one embodiment, the generator 15 is portable and attached to the beltof the patient 5. In other embodiments, the generator 15 isnon-portable. In some embodiments, the system 100 may include a chargingstation.

In one embodiment, the electrode assembly 10 is configured for bilateralstimulation of both the right and left supraorbital branches of theTrigeminal Nerve (V1) located above the eyebrows over the forehead. Theelectrode assembly may include both 2-contact and 4-contact electrodes.The contact areas from which the electrical stimulation will travel fromthe pulse generator to the patient will be placed on the forehead overthe V1 branch of the trigeminal nerve bilaterally. The regions ofcontact are arranged such that the electrical current travelsperpendicular to the two branches of the V1 branch between twoconductive areas (2 contact) or such that the current travels parallelto the two pathways of the V1 branch (4 contact).

In one embodiment, the electrode assembly 10 may be configured todeliver a symmetric biphasic pulse. In other embodiments, the pulsewaveform may be asymmetric and/or multiphasic.

The electrodes may be secured to the forehead by hypoallergenicbiocompatible hydrogels, such as DERMAFLOW® hydrogel (AxelgaardManufacturing Co, Ltd, Fallbrook, Calif., USA). Such gels have beenspecifically developed for use on the skin and forehead, to minimizeskin irritation, and have undergone ISO skin sensitization andhistocompatibility studies in animals.

The lead wires 40 carry the electrical impulse from the pulse generatorto the conductive regions of contact thereby delivering the prescribedstimulation. In one aspect, the lead wires are 13.5″ lead wires thatcarry the electrical impulse from the pulse generator to the conductiveregions of contact. The lead wires exit a single side of the pulsegenerator and will be bundled together. The lead wires terminate in aspecialized plug that connects to the pulse generator's socket, and isconfigured to prevent a patient-user from connecting the electrodes toother, potentially-hazardous sources of current.

In some embodiments, and as can be understood with reference to FIG. 4,the pulse generator 15 may also be used in conjunction with a physiciandocking/programming console. In other embodiments, the “programming”functions described herein may be performed directly via theuser-interface described elsewhere herein. The programming dockingconsole allows prescribing physicians to set parameters for theuser/patient and to monitor the patient's use since last docking event(e.g. by uploading of logfiles). When a patient-user visits theprescribing physician, the pulse generator 15 can be programmed toadminister the specific stimulation parameters prescribed by thephysician by using the console, such as pulse frequency. Theseparameters may be set individually, or the physician may select frompre-established combinations (of, e.g., repetition frequency, pulsewidth, on-period/off-period). The docking/programming station mayprovide for selection of these parameters from menus or offer step-wisesetting of parameters, within ranges and steps as allowed by the pulsegenerator 15. At follow-up visits, the logfiles may be examined toascertain actual patterns of device use, as this information may beuseful in treatment planning. These data may be displayed as text, ormay be presented graphically, for example, as a graph showing amounts ofdaily use. These data may be stored for the physician to incorporateinto the medical record for an individual patient.

For a more detailed discussion of the pulse generator, reference is nowmade to FIGS. 3A-3L, which illustrate various views of one exemplaryembodiment of the pulse generator, FIG. 4, which is a block diagramdepicting one embodiment of the pulse generator 15, and FIG. 5, which isa flow chart illustrating one embodiment of a method for operation ofthe pulse generator 15.

As can be understood from FIGS. 3A-3L, and with reference to FIGS. 4 and5, the pulse generator 15 comprises a sealed body or case 25 whichencloses or houses the internal components, such as the microcontrollerand battery discussed below, and other wiring and electronic components.The pulse generator may be manufactured by ITO Co., Ltd., Japan, orother suitable manufacturer.

The sealed body 25 protects the internal components and preventsliquids, etc. from penetrating the body and damaging internalcomponents. In one embodiment, the pulse generator 15 is housed in arectangular hard plastic case 25 with dimensions of approximately 115 mm(4.5 in) H×69 mm (2.7 in) W×27 mm (1.1 in) D and a weight of 145 gr (5.1oz) without a battery. In other embodiments, the body or case may bemade of a metallic alloy or a composite material. As shown in FIG. 3C,and others, the body 25 includes a front portion 26 and a back portion27. The front and back portion are sealingly engaged to prevent fluids,etc. from entering the body and interfering with the internal andelectrical components housed within the body. As shown in FIGS. 3D and3F-1, the body 25 may include raised features 28 configured to provide agripping surface by which a user, physician, etc. can open the pulsegenerator to, for example, replace a battery or other electricalcomponent. As can be seen in FIGS. 3A-3B and others, the pulse generator15 may also include user control features 30, e.g. buttons, that allowthe user to turn the power on and off or that provide a temporary lock.In some embodiments, the user control features 30 may be up and downarrow buttons that allow the patient-user to adjust the stimulusamplitude. In some embodiments, this is the only parameter which isuser-adjustable (all others are controlled via the physician'sprogramming).

As shown in FIGS. 3E-1, 3E-2, 3I-3K, and others, the pulse generator 15may also include at least one specialized socket or channel 35 forconnecting the lead wires of the electrodes. The channel 35 comprisesgrooves or openings 39 configured to accept an end of the lead wires ofthe electrode assembly. That is, the channel 39 is “keyed” for the endof the electrode or the electrode assembly. The end of the lead wire 12includes corresponding projections 39 a such that the projections 39 aare received in the grooves 39 in a lock and key type configuration.This lock and key configuration prevent a patient-user from connectingthe electrodes to other, potentially-hazardous sources of current andother incompatible electrode assemblies from being used with the pulsegenerator. In use, when a two-contact electrode is used, one channel 35is utilized. When a four contact electrode is used, two channels 35 areutilized.

As can be seen in at least FIGS. 3E-1 and 3E-2, the pulse generator 15may also include a power inlet port 36. The power inlet port 36 isconfigured to accept a connector from a power supply source, such as aDC power supply. In use, the pulse generator is powered by a batteryand/or the power supply source (not shown).

In some embodiments, the pulse generator 15 is powered by a rechargeablelithium-ion 9V battery that is received in a battery cavity 29 of thebody 25, as shown in at least FIGS. 3F-2, 3G and 3I. In someembodiments, the generator 15 is powered by lithium-polymer batteries.

As can be understood from FIGS. 3G, 3H, 31, 3K, 3L and others, the pulsegenerator 15 also includes a display 40, such as an LED or LCD screen,to display a graphical user interface (GUI). The display may also becontrolled by a microcontroller 126 on a display PCB 128. The displayPCB 128 is coupled to the pulse generator microcontroller 125 on themicrocontroller PCB 129 via a ribbon 127. The display 40 may bemanipulated by user control features 30 that allow the physician andpatient to select specific graphical menus. The user control features 30may be generated on the GUI or may be features of or integrated with thecase 25. The GUI may include a touch-screen interface, thereby allowingthe user-patient to make a selection by touching it on the screen.

The GUI is used to control the electric stimulation parameters and, insome embodiments, may provide password protection. In one embodiment,two levels of password protection are provided. The first level ofprotection allows patients to change their stimulation parameters withina range that has been predetermined by qualified medical personnel,which may be limited to electrical current amplitude. The second levelof password protection allows qualified medical personnel to limit therange of stimulation parameters available to the patient. In addition tothese parameters, qualified medical personnel can select timed therapyregimens of 1 to 16 hours, as well as a continuous stimulation mode.

As can be understood from FIG. 4, the pulse generator is coupled to apower source 100. With reference to FIGS. 3A-3L, in one embodiment, thepulse generator 15 is operably coupled to a battery 100. In otherembodiments, the power source may be any suitable power source, such asa fuel cell, or etc. In some embodiments, the battery 100 isrechargeable using inductive coupling to the patient's home basestation. In some embodiments, the rechargeable battery has a 5 yearlife. The battery 100 and/or the pulse generator 25 may be operablycoupled to a (an additional) power supply or charging station 115, suchas the patient's home base station. The battery may be an internallithium rechargeable battery. In one embodiment, the battery has acapacity up to 1000 mA-hours to last a minimum of 36-48 hours betweencharges. In some embodiments, the pulse generator may also be used inconjunction with the patient recharging station. In one embodiment, thepatient recharging station is a bedside stand and recharging facilityfor storing the device when not in use. The pulse generator 15 is alsooperably coupled to electrodes 105 (which may be a part of the electrodeassembly 10). In some embodiments, the pulse generator 15 may be coupledto the electrodes 105 via the wire 20 or the generator 15 and theelectrodes 105 may be wirelessly coupled. In some embodiments, theelectrodes 105 and the generator 15 may be a single unit, e.g. thegenerator 15 is connected directly to and positioned generally on theelectrode. The electrode 105 may be replaced daily (or at anotherappropriate time) but the generator 15 is reusable. In otherembodiments, the generator may be intended for a single-time use(non-reusable). The electrodes 105 may provide data to the pulsegenerator 15 and the generator 15 may, in turn, produce an output 120,such as notification to the patient that an electrode has becomedisconnected or that an electrode needs to be repositioned. In someembodiments, the pulse generator 15 may further include a digitaldisplay of some or all parameters including output current and skinimpedance. As indicated in FIG. 4, the pulse generator 15 is incommunication with a storage medium 110. In some embodiments, thestorage medium is integrated with the pulse generator. In someembodiments, the storage medium is a separate component of the system.The pulse generator 15 includes a microcontroller 125, or other suitableprocessor, for receiving and executing instructions from a storagemedium 110, such as a non-volatile storage medium, magnetic storagemedium, optical storage medium, flash memory, other computer readablemedium, or suitable memory device. A processor, such as themicrocontroller 125, may control operation of the pulse generator 15.The processor 125 may be any electronic device cable of processing,receiving and/or transmitting instructions. For example, the processor125 may be a microprocessor, a microcomputer and the like. Variousfeatures to be implemented by the programmable microcontroller 125 ofthe pulse generator 15 are discussed in more detail with reference toFIG. 5.

FIG. 5 is a flow chart illustrating one embodiment of a method 200 foroperating a pulse generator in accordance with the present disclosure.The method 200 may be performed by the microcontroller 125, or othersuitable processor executing instructions from a computer readablemedium. It should be appreciated that the operations of the method 200may be performed in the order illustrated, in another suitable orderand/or one or more operations may be performed simultaneously. Moreover,in some embodiments, the method 200 may include more or fewer operationsthan those illustrated.

In operation 205, the pulse generator may be turned on or otherwiseactivated. As part of this operation, the identity of the intendedrecipient of the treatment may be verified. That is, use of the pulsegenerator may be restricted to a specific individual patient for whichTNS treatment has been prescribed, and may not be used by otherunauthorized individuals. In some embodiments, a multi-digit personalcode (PIN) that may be chosen by the patient and set by the physician.In some embodiments, the PIN may be a 5 digit code. The patient entersthe PIN before treatment will begin. If there are more than apredetermined number of incorrect guesses (e.g. 5) of the PIN, thegenerator ceases to be operational (e.g. “locks up”) for 1 hour (orother appropriate time) and logs the event. In some embodiments, onlyone treatment session per day is permitted. In other embodiments, abiometric identification system (e.g. a thumbprint) may be used insteadof a PIN. The PIN or biometric ID prevent sharing of devices and mayreduce the risk of clinically inappropriate use by other individuals.

In operation 210, an electrode check is made. The electrode check may beperformed at the start of the session and may monitor the electrodeassembly for operational anomalies. In one embodiment, the pulsegenerator may include a “handshake” with a chip or circuit on orassociated with the electrode, which downloads a serial number, anddetects the model of electrode (e.g. a single pair of contacts orseparate R/L pairs of contacts). In the operation, the pulse generatorchecks to determine if it is connected to the electrodes, the electrodesare properly positioned and the like. In some embodiments, the pulsegenerator may further deliver stimulation signals to the electrodecontacts within an electrode assembly in this operation and may set the“used” bit on the electrode assembly at the end of treatment to enforcesingle use. This ensures that the gel on the contacts is uncontaminated,as damaged gel could produce current flow irregularities (“hot spots”)leading to skin injury from excessive local current flow. If theelectrode check is ok (e.g. the electrodes are connected, properlypositioned and the like), then the method may proceed to operation215-pulse generation.

If the electrode check is not ok, then the method proceeds to operation212. For example, if impedance suddenly becomes high, then a signal willbe sent to indicate that the electrodes have become disconnected(“infinite” impedance). If impedance is low or excessively low, then theuser is prompted to relocate the electrodes (e.g. there is a need toreposition the electrode to ensure skin safety). In some embodiments,the signal may also be sent or alternatively sent to a physician orother care provider and/or a designated family member. The pulsegenerator may signal such trouble conditions. Treatment may beterminated or the patient may adjust the electrodes as indicated andrestart treatment (e.g. turning the pulse generator off and then back onor the pulse generator may perform another electrode check).

The method 200 may next proceed to operation 215. A pulse may begenerated in this operation. The pulse characteristics may include: (1)controlled-current rectangular pulses, to one or two channels, with oneor more of the following characteristics: (a) maximum deliverablecurrent of 30 mA/channel (or as defined elsewhere in this disclosure),(b) physician may set upper and lower bounds for each patient, rangingfrom 0.3 to 30 mA (e.g. default settings of 1 mA lower bound, 20 mAupper bound), (c) user-adjustment of actual current delivery within thatrange to allow setting for comfort, (d) provision for a single bipolarchannel, with user ability to swap polarity (e.g. shift from “rightside=positive/left side=negative” to the opposite) and (e) provision fora pair of bipolar channels with user ability to swap polarity (e.g.right and left channels are separate pairs, each with a lower and upperelectrode contact, and options are “upper pos./lower neg.” and “lowerpos./upper neg.” arrangements); (2) pulse width (duration) from 10 to3000 μs, which may be set by physician (e.g. default 250 μs); (3)repetition rate frequency ranging from 10 to 300 Hz, which may be set byphysician; (4) duty cycle adjustable by physician, setting the secondson and seconds off periods, each variable from 5 s to 60 s in, forexample, 5 s steps (e.g. default 30 s on/30 s off); and (5) sessionlength of 1 to 23 hours (e.g. default 8 hours). Various embodiments maypermit adjustment or programming of any or all of the foregoing. In someembodiments, the operation includes 2-channels, and operates at thefollowing parameters: frequency 1-300 Hz, pulse duration 50-500 μs, dutycycle 1-100%. The two channels may be configured to provide eithersynchronous or asynchronous stimulation. In some embodiments, the pulsegenerated in this operation may be transmitted across two separatechannels or multiple unique pulses may be generated and carried across aseparate channel. In some embodiments, the pulse wave form may be shapedthrough programmable settings for pulse duration, frequency, and dutycycle and the like. These programmable settings may be adjusted only bya physician or other authorized caregiver in certain embodiments.Generally, reprogramming of operational parameters discussed herein maybe restricted to parties supplying an appropriate password or othercredential, such as a biometric indicator. This feature may preventpatients from using the generator at settings contrary to medicalprescription or outside of FDA labeling.

As can be understood from the previous section, the programmablemicrocontroller 125 limits output current. That is, thepatient-adjustable current is limited to approximately less than 35 mAto maximize tolerance, minimize current and charge density, and minimizeany potential for current penetration through the skull. The controller125 may deliver true square-wave charge-balanced output. This may beadvantageous because existing commercial TENS units have asymmetricoutput, resulting in irregular stimulation, and risk for formation ofhotspots, which may contribute to skin irritation or injury. In someembodiments, asymmetric waveforms may be employed, provided the specificsignals are safe.

The microcontroller may be set to a range of outputs. In one embodiment,the range may be set to approximately between 2.5 mA and approximately 7mA. In one embodiment, the microcontroller limits the output current toapproximately 7 mA, and the patient may adjust the current within arange below 7 mA. In another embodiment, the microcontroller can limitthe output current to a narrow range (e.g. to ensure safety andcompliance) of between approximately 2.5 mA to approximately 5 mA usingan external electrode two or four contact electrode. In this way, thepatient is prevented from delivering current at too high or too low ofan output. In still another embodiment, the output current may belimited to an exact current, e.g. 5 mA, up to a maximum of a fixedcurrent of 7 mA, depending on the size, resistance, or impedance of theelectrode. In another embodiment, the output current is limited to arange not to exceed 10 mA, 7 mA, or 5 mA. Without wishing to be limitedby any particular theory, it is believed that higher currents, dependingon the size and impedance of the electrode, may cause pain, discomfortand/or skin irritation for the patient.

The method 200 may further include an operation 220 in which theactivity of the pulse generator is logged. The logging of use operation220 may include: (1) recording data for each session, such as: (a)session start date-and-time; (b) session stop date-and-time (actual timetreatment was ended), (c) user-adjustable setting (e.g. actual currentdelivered), and (d) session-specific data (e.g. max & min impedance,electrode & configuration). The operation 220 may also include: loggingoperational anomalies (e.g. electrode disconnects, low impedances,lock-outs for attempts at unauthorized use, etc.), transferring data tothe physician's programming console and may include the capacity tostore 6 months of treatment data. In other embodiments, less than 6months or greater than 6 months of data may be stored. A patient'scompliance (adherence) and usage is monitored via, e.g., logfiles. Suchmonitoring may be used to help monitor use patterns in assessing apatient's response to treatment (e.g., a poor clinical response may belinked to using the device less often than prescribed).

In some embodiments, the pulse generator may also signal operationalparameters to the patient. This may be part of the logging of useoperation 220 or may be part of a different or a separate operation. Forexample, a signal may be sent if the user is locked out for PINguessing, a signal may indicate the minutes until the generator isunlocked. In another example, a signal may be sent if the need forphysician follow-up reprogramming is coming up and the signal indicateshow many more days of treatment remain before a “refill” date isreached. The pulse generator may also display current time and date inthe time zone where programmed, display time left in current session(hr:min) and/or display time needed in charger (hr:min) to be ready forthe next session.

The method 200 may further include an operation 225 in which the end ofthe authorized treatment period is signaled. In one embodiment, severalweeks (e.g. default is 3 weeks) prior to the end of the treatment period(e.g. default is 3 months), the operation 230 notifies the user that thetreatment period is nearing its end and that a follow up visit with theprescribing doctor for clinical assessment and reprogramming needs to bescheduled. In one embodiment, notification is made at the start of thesession. In subsequent weeks, the patient is notified that one less weekremains to schedule the visit. In the final week, a daily count-down ofdays remaining is provided. At the final treatment in the authorizedperiod, the user is notified that this is the last treatment.

In operation 230, treatment is terminated. Use of the generator may besuspended (e.g. user is locked out) until reprogrammed by a physician orphysician programming console or use of the generator may be terminated.

In use, in one embodiment, the electrode assembly 10 is positioned overthe forehead of the patient 5. In some embodiments, the electrodeassembly 10 may include an insulative connection region which helps toline up the assembly 10 with the midline of the nose of the patient 5.In some embodiments, the electrode assembly 10 is placed over thesupraorbital foramina, located over the orbital ridge approximately2.1-2.6 cm lateral to nasal midline. In one embodiment, the electrodeassembly 10 is then connected to a pulse generator 15 via the electricalcable 20. In other embodiments, the electrode assembly is connected tothe pulse generator 15 via a wireless connection. In some embodiments,the electrode assembly may be a subcutaneous or percutaneous implantableelectrode assembly. In the “percutaneous” form, the electrodes areinserted through the skin but the generator remains external; there maybe a lead wire which exits through the skin, or the electrode may beentirely within the skin tissue and they are coupled to a non-implantedgenerator through, e.g., inductive coupling. The pulse generator thenprovides stimulation according to methods as described herein.

As indicated above, the pulse generator disclosed herein may be used totreat a disorder or condition in a patient using trigeminal nervestimulation (TNS). Broadly speaking, the method of treatment includespositioning external electrodes over or near at least one of theforamina or branches of the trigeminal nerve (FIG. 1A-1B), andstimulating the electrodes using a stimulator or pulse generator asdisclosed herein for a fixed time at specified operational parameters.In one embodiment, the external electrodes are positioned over theforamina of the supraorbital or ophthalmic nerves (FIG. 1A, Foramen 1).In alternative embodiments, the electrode assembly 10 can be positionedover the foramina of the maxillary nerves (FIG. 1A, Foramen 2) or themandibular nerves (FIG. 1B, Foramen 3). In yet other embodiments, thestimulation can be unilaterally applied to one foramen of the trigeminalnerves. In other embodiments, electrodes may be positioned at a regionof the patient's face (on the right and/or left side) corresponding withthe supratrochlear nerve, infratrochlear nerve, zygomaticotemporal,zygomaticofacial, zygomaticoorbital, mentalis, nasal and/orauriculotemporal nerves and/or their respective foramina. In otherembodiments, subcutaneous implantable electrodes may be used with thepulse generator as disclosed herein. The programmable microcontrollermay be programmed to operate at one or more of the following parameters.

In various embodiments, the stimulation is delivered at a specific pulsewidth or range of pulse widths (or pulse duration). The stimulation canbe set to deliver pulse widths in the range greater than and/or lessthan one or more of 50 μs, 60 μs, 70 μs, 80 μs, 90 μs, 100 μs, 125 μs,150 μs, 175 μs, 200 μs, 225 μs, 250 μs, up to 500 μs. Those of skill inthe art will recognized that one or more of the above times can be usedas a border of a range of pulse widths.

In some embodiments, the stimulation amplitude is delivered as a voltageor current controlled stimulation. In other embodiments it can bedelivered as a capacitive discharge. In various embodiments, the currentamplitude can be in any range within a lower limit of about 300 μA andan upper limit of about 30 mA-35 mA, depending on the surface area ofthe electrodes, inter-electrode distance, the branch(es) stimulated, andthe modeling data as described above. In various embodiments, theamplitude can be in a range greater than and/or less than one or more of50 μA, 75 μA, 100 μA, 125 μA, 150 μA, 175 μA, 200 μA, 225 μA, 250 μA,275 μA, 300 μA, 325 μA, 350 μA, 375 μA, 400 μA, 425 μA, 450 μA, 475 μA,500 μA, 525 μA, 550 μA, 575 μA, 600 μA, 625 μA, 650 μA, 675 μA, 700 μA,725 μA, 850 μA, 875 μA, 900 μA, 925 μA, 950 μA, 975 μA, 1 mA, 2 mA, 3mA, 4 mA, 5 mA, 6 mA, 7 mA, 8 mA, 9 mA, 10 mA, 11 mA, 12 mA, 13 mA, 14mA, 15 mA, 16 mA, 17 mA, 18 mA, 19 mA and 20 mA. In some embodiments,the current amplitudes are less than 7 mA, or less than 6 mA, dependingon the size, impedance, resistance, or configuration of theelectrode(s). In some embodiments, the current amplitude is betweenabout 2.5 mA and about 5 mA. Those of skill in the art will recognizethat one or more of the above amplitudes can be used as a border of arange of amplitudes.

In various embodiments, the stimulation can be delivered at one or morefrequencies, or within a range of frequencies. The stimulation can beset to be delivered at frequencies less than, and/or greater than one ormore of 50 Hz, 45 Hz, 40 Hz, 35 Hz, 30 Hz, 25 Hz, 20 Hz, 15 Hz, or 10Hz. In various embodiments, the stimulation can be set to be deliveredat frequencies greater than, and/or less than, one or more of 20 Hz, 30Hz, 40 Hz, 50 Hz, 60 Hz, 70 Hz, 80 Hz, 90 Hz, 100 Hz, 120 Hz, 125 Hz,150 Hz, up to 300 Hz. Those of skill in the art will recognize that oneor more of the above frequencies can be used as a border of a range offrequencies.

In various embodiments, the stimulation is delivered at a specific dutycycle or range of duty cycles. The stimulation can be set to bedelivered at a duty cycle in the range greater than and/or less than oneor more of 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%. In some embodiments, toensure preservation of the nerve, a duty cycle of 10% to 50% may bepreferable. In some embodiments, duty cycles up to 100% may be useful inparticular circumstances. Those of skill in the art will recognize thatone or more of the above percentages can be used as a border of a rangeof duty cycles.

All directional references (e.g., proximal, distal, upper, lower,upward, downward, left, right, lateral, front, back, top, bottom, above,below, vertical, horizontal, clockwise, and counterclockwise) are onlyused for identification purposes to aid the reader's understanding ofthe present invention, and do not create limitations, particularly as tothe position, orientation, or use of the invention. Connectionreferences (e.g., attached, coupled, connected, and joined) are to beconstrued broadly and may include intermediate members between acollection of elements and relative movement between elements unlessotherwise indicated. As such, connection references do not necessarilyinfer that two elements are directly connected and in fixed relation toeach other. The exemplary drawings are for purposes of illustration onlyand the dimensions, positions, order and relative sizes reflected in thedrawings attached hereto may vary.

The above specification and examples provide a complete description ofthe structure and use of exemplary embodiments of the invention.Although various embodiments of the invention have been described abovewith a certain degree of particularity, or with reference to one or moreindividual embodiments, those skilled in the art could make numerousalterations to the disclosed embodiments without departing from thespirit or scope of this invention. Other embodiments are thereforecontemplated. It is intended that all matter contained in the abovedescription and shown in the accompanying drawings shall be interpretedas illustrative only of particular embodiments and not limiting. Changesin detail or structure may be made without departing from the basicelements of the invention as defined in the following claims.

What is claimed is:
 1. A system for nerve stimulation, comprising: apulse generator comprising: a user control configured to receive a useradjustment; and a microcontroller configured to: receive electricstimulation parameters comprising at least one user-set parameter and atleast one physician-set parameter, the at least one user-set parametercomprising a current amplitude responsive to the user adjustment of theuser control, and the at least one physician-set parameter comprising anupper bound and a lower bound for the current amplitude; and operate thepulse generator to produce electrical pulses according to the electricstimulation parameters during a treatment session.
 2. The system ofclaim 1, further comprising an electrode assembly communicativelycoupled to the pulse generator.
 3. The system of claim 2, wherein theelectrode assembly is coupled to the pulse generator by a connector or alead wire, or wirelessly coupled to the pulse generator.
 4. The systemof claim 2, wherein the electrode assembly comprises two contacts. 5.The system of claim 2, wherein the microcontroller is further configuredto detect a model of the electrode assembly.
 6. The system of claim 2,wherein the microcontroller is further configured to set a used bit onthe electrode assembly at the end of the treatment session.
 7. Thesystem of claim 1, wherein the microcontroller is further configured torecord a log of use for monitoring a patient's adherence to a treatmentplan, wherein the log includes a duration of the treatment session, astart time for the treatment session, an end time for the treatmentsession, a setting for the at least one user-set parameter for thetreatment session, and/or an impedance for the treatment session.
 8. Thesystem of claim 1, wherein the electric stimulation parameters comprisea current amplitude between 0.3 and 30 mA, a frequency between 1 and 300Hz, a pulse duration between 50 and 500 microseconds, and a duty cyclebetween 1 and 100%.
 9. The system of claim 1, further comprising a powersource.
 10. The system of claim 9, wherein the power source comprises abattery electrically coupled to the pulse generator.
 11. The system ofclaim 1, further comprising a power supply or a charging station.
 12. Amethod for nerve stimulation, comprising: receiving, by a pulsegenerator, electric stimulation parameters comprising at least oneuser-set parameter and at least one physician-set parameter, the atleast one user-set parameter comprising a current amplitude responsiveto a user adjusting a user control, and the at least one physician-setparameter comprising an upper bound and a lower bound for the currentamplitude; and producing, by the pulse generator, electrical pulsesaccording to electric stimulation parameters during a treatment session.13. The method of claim 12, further comprising applying, by an electrodeassembly communicatively coupled to the pulse generator, the electricalpulses to at least one branch of a patient's trigeminal nerve.
 14. Themethod of claim 13, wherein the applying is performed using a connectoror a lead wire coupling the electrode assembly and the pulse generator,or using a wireless connection coupling the electrode assembly and thepulse generator.
 15. The method of claim 13, wherein the applying isperformed via two contacts provided by the electrode assembly.
 16. Themethod of claim 13, further comprising detecting a model of theelectrode assembly.
 17. The method of claim 13, further comprisingsetting a used bit on the electrode assembly at the end of the treatmentsession.
 18. The method of claim 12, further comprising recording, bythe pulse generator, a log of use of for monitoring a patient'sadherence to a treatment plan, wherein the log includes a duration ofthe treatment session, a start time for the treatment session, an endtime for the treatment session, a setting for the at least one user-setparameter for the treatment session, and/or an impedance for thetreatment session.
 19. The method of claim 12, wherein the electricpulses have a current amplitude between 0.3 and 30 mA, a frequencybetween 1 and 300 Hz, a pulse duration between 50 and 500 microseconds,and a duty cycle between 1 and 100%.
 20. The method of claim 12, furthercomprising supplying, by a power source electrically coupled to thepulse generator, power to the pulse generator.